Process for producing sesamol



ilnite Stats tic York

No Drawing. Filed Feb. 8, 1960, Ser. No. 7,118

12 Claims. (Cl. 260340.5)

This invention relates to the production of sesamol and more particularly to processes for and intermediates involved in the synthesis of sesamol.

Sesamol is useful as an antioxidant in edible fats. Budowski of the Southern Regional Research Laboratory found that the antioxidant activity of sesamol at a level of 0.01% in lard is comparable with the same concentration in lard of nordihydroguaiaretic acid and that the antioxidant efliciency of sesamol continues to increase With increasing concentrations, even at comparatively high levels (Journal of the American Oil Chemists Society, 27, 264267, July 1950). This is in marked contrast to the action of a-tocopherol which attains a maximum protective efliciency at about 0.05% concentration.

Although sesamol may be obtained from sesame oil, the procedure is time consuming with relatively small yields. In 1936, Boeseken et al. described the production of sesamol synthetically from piperonal, using peracetic acid as the oxidizing agent. No significant work on the synthetic production of sesamol has been published since the appearance of the study of Boeseken and his associates.

While Boeseken et al. reported a quantity of sesamol obtained which represented a yield of about 60%, repeated conduct of the Boeseken et al. procedure failed to produce a yield of sesamol greater than the order of 30 to 35%. In the Boeseken procedure, a distillation step was necessary in order to obtain pure sesamol.

In accordance with this invention, sesamol is produced synthetically from piperonal in yields of the order of 70% 1 Moreover, no distillation step is required to produce pure sesamol.

The processes of this invention involve reacting in a substantially non polar Water-insoluble organic solvent piperonal with a percarboxylic acid to form sesamyl formate. This formate upon hydrolysis produces a Watersoluble salt of sesamol. Sesamol is recovered from this water-soluble salt. Desirably, the water immiscible organic solvent has a boiling point less than 200 C. and preferably less than 150 C. The reaction may be conducted at a temperature within the range of l0 to 50 C. and preferably Within the range of 5 to 15 C. The water soluble salt of sesamol is desirably an alkali metal salt of sesamol and is formed in a non-oxidizing atmosphere, such as nitrogen. The alkali metal salt or other water soluble salt of sesamol is hydrolized, preferably in the presence of a phenol stabilizing agent, such as an alkali metal hydrosulfite, and sesamol is recovered. Examples of percarboxylic acids which may be employed are peracetic acid, monoperphthalic acid, performic acid, perpropionic acid, perbutyric acid, perbenzoic acid, monopercamphoric acid or monopersuccinic acid. Monoperphthalic acid possesses advantages in that it is more stable and, under particular conditions, easier and cheaper to prepare than peracetic acid, for example. Although sodium hydrosulfite, also sometimes called sodium dithionite and sodium hyposulfite, is a preferred phenol stabilizing agent, examples of other agents which may be used in the practise of this invention are: sulfur dioxide, titanous sulfate, sodium sulfite and sodium bisulfite.

Examples of the substantially non polar, Water immiscible organic solvents are aromatic hydrocarbons, such as toluene and benzene, xylene, straight chained or branched alkanes, halogenated aliphatic and aromatic hydrocarbons, such as chlorobenzenes.

Sesamol is conveniently produced by reacting in toluene piperonal With peracetic acid at 5 to 15 C. in the presence of a water binding agent such as sodium sulfate and sodium acetate to bind the Water present in technical grade peracetic acid. This oxidation step requires about 4 to 16 hours. The toluene solution containing the reaction product may be washed with ice Water. After washing, there is added a solution of an alkali metal or alkaline earth metal hydroxide, such as sodium hydroxide, and the addition is conducted in a non-oxidizing atmosphere such as nitrogen. The Water immiscible solvent, toluene, is separated from the solution of the metallic sesamate such as sodium sesamate and the unreacted piperonal may be obtained from the toluene by distillation. The metallic sesarnate, such as sodium sesamate, is neutralized to a pH of about 8.3. It is essential that the non-oxidizing atmosphere be maintained as long as the solution of the metallic sesamate remains in an alkaline condition (above about pH 8.3). Solid carbon dioxide is particularly adapted for hydrolyzing the metallic sesamate and neutralizing effectively the excess alkali; it creates a nonoxidizing atmosphere; and finally, produces the low temperature at which the reaction is desirably conducted. The liberated sesamol is then extracted with a water immiscible solvent such as toluene. The water immiscible solvent extract is then separated from the aqueous solution and the sesamol recovered in relatively pure form from the Water immiscible extract.

A more comprehensive understanding of this invention is obtained by reference to the following example:

Example There is stirred in a glass-lined kettle 250 cc. of toluene and 200 g. peracetic acid. The mixture is cooled in an ice bath to an inside temperature of about +5 C. In order to bind, at lea-st partially, the approximately 15% water content contained in technical peracetic acid, there are added to the mixture 5 g. of sodium acetate and g. of anhydrous sodium sulfate. The solution of the peracetic acid in the toluene is stirred and while being stirred, there is introduced dropwise a solution maintained at 1520 C. of g. of piperonal (1 mole) in 250 cc. of toluene. The addition is completed within 1 hour and the temperature of the mixture is gradually raised to 1520 C. In the course of this oxidation, the initially colorless mixture becomes gradually first, lemon colored, and then, distinctly yellow colored. Stirring is continued and the reaction mixture is maintained at a temperature below 20 C. Finally, stirring is continued over night. The next morning, an additional 500 cc. of pure toluene is added and the reaction mixture is washed with four 300 cc. portions of ice water. The washings involve adding the ice-cold water to the mixture, stirring it for 10 minutes, then stopping the stirring and allowing the two layers to separate before separation of the aqueous washings. These washings contain substantially acetic acid and minor amounts of strongly colored impurities. The color of the washing is usually amber.

If desired, the sesamyl formate may be isolated by subjecting the toluene solution containing the ester to a low temperature (e.g., 30 C.) The sesamyl formate crystallizes and may be obtained by decantation. It may be purified by redissolving in toluene and recrystallizing at low temperatures.

If sesamyl formate is not isolated at this point, 3 g. of sodium hydrosulfite is added and the surface of the mixture flushed by a nitrogen blanket. There is then introduced 1000 cc. of a 10% ice-cold sodium hydroxide solution. A minimum of 2 moles of sodium hydroxide is required; it is desirable to add about 2.5 moles in order to make sure that no free formic acid is present in the reaction mixture. The mixture is stirred for two hours at a temperature below 20 C. before allowing complete separation of the layers. The pH at this point is higher than 9.0. The separated toluene layer itself is dried through the addition of a small amount of anhydrous sodium sulfate, filtered, and the toluene recovered by distillation in vacuo. The residue of this distillation is a white oil which readily crystallizes to recoverable 23 g. of piperonal.

The aqueous layer is lowered and in a separate container 500 cc. of fresh toluene and solid pieces of Dry Ice are added to it under occasional stirring until the pH of the mixture has reached 8.3. The toluene layer on the top of the cold aqueous layer which is acidified by action with the solid carbon dioxide is now decanted and 300 cc. of toluene is added and the mixture stirred again. After decantation of this toluene layer, a final 200 cc. portion of toluene is employed for the third extraction. The combined toluene layers are dried over anhydrous sodium sulfate, filtered, and the solvent recovered by vacuum distillation. The residue of this toluene distillation is about 90-105 grams of essentially pure sesamol, crystallizing immediately upon evaporation of the solvent. The sesamol obtained has a melting point of 645 C. The yield of sesamol is better than 70% of the theoretical and, in addition, about 15% of the piperonal is recovered. The recovered piperonal may be used directly in a subsequent batch without further purification.

The reaction product of piperonal and peracetic acid is sesamyl formate which, upon isolation, is found to be crystalline and have a melting point of 29-30 C. It is very readily hydrolyzed and autodecomposes even in the presence of atmospheric moisture. For most purposes, it is desirable to proceed with hydrolysis of this intermediate and isolate only the desired end product, sesamol.

What is claimed is:

1. The process of producing sesamol which comprises reacting in a non polar, water immiscible organic solvent piperonal with a percarboxylic acid.

2. The process of producing sesamol which comprises reacting in a non polar, water immiscible organic solvent piperonal with a percarboxylic acid to produce a carboxylic ester of sesamol, forming with said ester a water soluble salt of sesamol and recovering sesamol from said water soluble salt.

3. The process of producing sesamol which comprises reacting in a non polar, water immiscible organic solvent having a boiling point less than 200 C. piperonal with a percarboxylic acid at a temperature of l0 to 50 C. to produce a carboxylic ester of sesamol, forming with said ester in a non-oxidizing atmosphere an aqueous solution of a water soluble salt of sesamol neutralizing said water soluble salt and recovering sesamol from the resulting product.

4. The process of producing sesamol which comprises reacting in a non polar, water immiscible organic solvent having a boiling point of less than 150 C. piperonal with a percarboxylic acid at a temperature of 5 to 15 C. to produce a carboxylic acid ester of sesamol, forming with said ester in a non-oxidizing atmosphere an aqueous solution of an alkali metal salt of sesamol, neutralizing said water soluble salt in the presence of a phenol stabilizing agent and recovering sesamol from the resulting product.

5. The process of producing sesamol in accordance with claim 4, in which the percarboxylic acid is peracetic acid.

6. The process of producing sesamol in accordance with claim 4, in which the non polar, water immiscible organic solvent is an aromatic hydrocarbon.

7. The process of producing sesamol in accordance with claim 4, in which the percarboxylic acid is monoperphthalic acid.

8. The process of producing a water soluble salt of sesamol which comprises reacting in a non polar, water immiscible organic solvent having a boiling point below 200 C. piperonal with a percarboxylic acid at a temperature of -l0 to 50 C. and reacting the carboxylic ester of sesamol produced with the required base to produce the water soluble salt of sesamol.

9. In a process of producing sesamol, the step comprising adding solidcarbon dioxide to a water soluble salt of sesarnol to liberate sesamol therefrom at a low temperature in a non-oxidizing atmosphere.

10. In a process of producing sesamol, the step comprising adding solid carbon dioxide to an alkali metal sesamate to liberate sesamol therefrom at a low temperature in a non-oxidizing atmosphere.

11. In a process of producing sesamol, the steps comprising adding solid carbon dioxide to sodium sesamate to liberate sesamol therefrom at a low temperature in a non-oxidizing atmosphere and recovering the liberated sesamol.

12. The process of producing sesamol which comprises reacting in toluene piperonal with peracetic acid at 5 to 15 C. in the presence of sodium sulfate and sodium acetate, washing the toluene solution of the reaction prodnet with ice water, adding in an atmosphere of nitrogen an ice-cold, concentrated aqueous solution of sodium hydroxide to produce sodium sesamate, separating the solution of sodium sesamate from the toluene, distilling the toluene after separation to recover the unreacted piperonal, neutralizing the sodium sesamate solution with excess of solid carbon dioxide to a pH of 8.3, extracting the resulting sesamol with toluene, separating the toluene extract from the aqueous solution and recovering sesamol from the toluene extract.

References Cited in the file of this patent UNITED STATES PATENTS Hardwicke et al May 5, 1959 OTHER REFERENCES 

1. THE PROCESS OF PRODUCING SESAMOL WHICH COMPRISES REACTING IN A NON POLAR, WATER IMMISCIBLE ORGANIC SOLVENT PIPERONAL WITH A PERCARBOXYLIC ACID. 